Skip to main content
Log in

The relevance of 4,5-dihydroxy-2-hexanone in the excretion kinetics ofn-hexane metabolites in rat and man

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Male Wistar rats were exposed ton-hexane concentrations between 50 and 3000 ppm for 8 h, and urinary excretion kinetics of then-hexane metabolites 1-hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 2,5-hexanedione, and 4,5-dihydroxy-2-hexanone were assessed. The amounts of metabolites excreted were linearly dependent on then-hexane exposure concentration, up to an exposure of about 300 ppm. Above 300 ppm exposure the metabolite excretion indicated saturation kinetics in the metabolism ofn-hexane. In its quantity, the newly described 4,5-dihydroxy-2-hexanone was the second metabolite, its amount in the urine being about ten times higher than that of excreted 2,5-hexanedione. Using gas chromatography-mass spectrometry the occurrence of 4,5-dihydroxy-2-hexanone as ann-hexane metabolite in urine of man was confirmed after exposure of a male volunteer to a mean of 217 ppmn-hexane for 4 h (laboratory exposure). Twenty-six hours after starting this exposure the excretion of 4,5-dihydroxy-2-hexanone (as a result of then-hexane exposure) reached a level which was four times higher than the excretion of 2,5-hexanedione. The results in both rat and man indicate the relevance of 4,5-dihydroxy-2-hexanone as a metabolite ofn-hexane metabolism. Formation of this metabolite may be viewed as a route of detoxification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abou-Donia MB, Makkawy H-AM, Graham DG (1982) The relative neurotoxicities ofn-hexane methyln-butyl ketone, 2,5-hexanediol, and 2,5-hexanedione following oral or intraperitoneal administration in hens. Toxicol Appl Pharmacol 62: 369–389

    Google Scholar 

  • ACGIH (1986) In: Documentation of the threshhold limit values and the biological exposure indices, 5th edition, p. BEI-15-17 American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio, USA

  • Altenkirch H, Mager J, Stoltenburg G, Helmbrecht J (1977) Toxic polyneuropathies after sniffing a glue thinner. J Neurol 214: 137–152

    Google Scholar 

  • De Caprio AP, O'Neill EA (1985) Alterations in rat axonal cytoskeletal proteins induced by in vitro and in vivo 2,5-hexanedione exposure. Toxicol Appl Pharmacol 78: 235–247

    Google Scholar 

  • DiVincenzo GD, Kaplan CJ, Dedinas J (1976) Characterization of the metabolites of methyln-butyl ketone, methyl iso-butyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance. Toxicol Appl Pharmacol 36: 511–522

    Google Scholar 

  • DiVincenzo GD, Hamilton ML, Kaplan CJ, Dedinas J (1977) Metabolic fate and disposition of14C-labeled methyln-butyl ketone in the rat. Toxicol Appl Pharmacol 41: 547–560

    Google Scholar 

  • Fedtke N, Bolt H (1986a) Methodological investigations on the determinations ofn-hexane metabolites in urine. Int Arch Occup Environ Health 57: 149–158

    Google Scholar 

  • Fedtke N, Bolt HM (1986b) Detection of 2,5-hexanedione in the urine of persons not exposed ton-hexane. Int Arch Occup Environ Health 57: 143–148

    Google Scholar 

  • Fedtke N, Bolt HM (1987) 4,5-Dihydroxy-2-hexanone: a new metabolite ofn-hexane and of 2,5-hexanedione in rat urine. Biomed Environ Mass Spectrom (in press)

  • Frommer U, Ullrich V, Staudinger H-J (1970) Hydroxylation of aliphatic compounds by liver microsomes, I: the distribution pattern of isomeric alcohols. Z Physiol Chem 351: 903–912

    Google Scholar 

  • Frommer U, Ullrich V, Staudinger H-J (1972) The monooxygenation ofn-heptane by rat liver microsomes. Biochem Biophys Acta 280: 487–494

    Google Scholar 

  • Frommer U, Ullrich V, Orrenius S (1974) Influence of inducers and inhibitors on the hydroxylation pattern ofn-hexane in rat liver microsomes. FEBS Lett 41: 14–16

    Google Scholar 

  • Genter MB, Szakal-Quin G, Anderson CW, Anthony DC, Graham DG (1987) Evidence that pyrrole formation is a pathogenic step in γ-diketone neuropathy. Toxicol Appl Pharmacol 87:351–362

    Google Scholar 

  • Herskowitz A, Ishii N, Schaumburg H (1971) n-Hexane neuropathy: a syndrome occuring as a result of industrial exposure. N Engl J Med 285: 82–85

    Google Scholar 

  • Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1983a) A study on biological monitoring of n-hexane exposure. Int Arch Occup Environ Health 51: 253–260

    Google Scholar 

  • Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1983b) Changes ofn-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. Int Arch Occup Environ Health 53: 1–8

    Google Scholar 

  • Krasavage WJ, O'Donoghue JL, DiVincenco GD, Terhaar CJ (1980) The relative neurotoxicity of methyln-butyl etone,n-hexane and their metabolites. Toxicol Appl Pharmacol 52: 433–441

    Google Scholar 

  • Mutti A, Falzoi M, Lucertini S, Arfini G, Zignani M, Lombardi S, Franchini I (1984)n-Hexane metabolism in occupationally exposed workers. Br J Ind Med 41: 533–538

    Google Scholar 

  • Perbellini L, Brugnone F, Pastorello G, Grigolini L (1979) Urinary excretion ofn-hexane metabolites in rats and humans. Int Arch Occup Environ Health 42: 349–354

    Google Scholar 

  • Perbellini L, Brugnone F, Faggionato G (1981a) Urinary excretion of the metabolites ofn-hexane and its isomers during occupational exposure. J Ind Med 38: 20–26

    Google Scholar 

  • Perbellini L, Brugnone F, Silvestri R, Gafturi E (1981b) Mesurement of the urinary metabolites ofn-hexane, cyclohexane and their isomers by gas chromatography. Int Arch Occup Environ Health 48: 99–106

    Google Scholar 

  • Perbellini L, Amantini MC, Brugnone F, Frontali N (1982) Urinary excretion ofn-hexane metabolites. A comparative study in rat, rabbit and monkey. Arch Toxicol 50: 203–215

    Google Scholar 

  • Perbellini L, Tagliaro F, Maschio S, Zedde A, Brugnone F (1986) Dossagio gas-chromatographico del 2,5-esandione nelle urine. Med Lav 77: 628–634 (Italian with English summary)

    Google Scholar 

  • Schaumburg HH, Spencer PS (1976) Degeneration in central and peripheral nervous systems produced by puren-hexane: an experimental study. Brain 99: 183–192

    Google Scholar 

  • Towfighi J, Gonatas NK, Pleasure D, Cooper HS, McCrea L (1976) Glue sniffer's neuropathy. J Neurol 26: 238–243

    Google Scholar 

  • White EL, Bus JS, Heck H d'A (1979) Simultaneous determination ofn-hexane, 2-hexanone and 2,5-hexanedione in biological tissues by gas chromatography mass spectrometry. Biomed Mass Spectrom 6: 169–172

    Google Scholar 

  • Yamada S (1967) Intoxication polyneuritis in the workers exposed ton-hexane. Jpn J Ind Health 9: 651 (Japanese with English summary)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fedtke, N., Bolt, H.M. The relevance of 4,5-dihydroxy-2-hexanone in the excretion kinetics ofn-hexane metabolites in rat and man. Arch Toxicol 61, 131–137 (1987). https://doi.org/10.1007/BF00661371

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00661371

Key words

Navigation